scholarly journals Redefining Phenotypes to Advance Psychiatric Genetics: Implications from Hierarchical Taxonomy of Psychopathology

2018 ◽  
Author(s):  
Monika Waszczuk
Keyword(s):  
Statistical Power ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Large Body ◽  
Twin Studies ◽  
Higher Order ◽  
Assessment Tools ◽  
Risk Scores ◽  
General Factor ◽  
Genetic Covariance

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher-order psychopathology (e.g. the general factor), whereas other genes conferring more specific risk for individual spectra (e.g. internalizing), subfactors (e.g. fear disorders), or narrow symptoms (e.g. mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher-order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses.

scholarly journals Genetic contributions to suicidal thoughts and behaviors

2021 ◽  
pp. 1-8
Author(s):  
Emily DiBlasi ◽  
Jooeun Kang ◽  
Anna R. Docherty
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Molecular Genetic ◽  
Risk Scores ◽  
Major Depressive ◽  
Suicidal Thoughts ◽  
Genetic Covariance ◽  
Molecular Studies ◽  
And Behaviors ◽  
Suicidal Thoughts And Behaviors

Abstract Suicidal ideation, suicide attempt (SA) and suicide are significantly heritable phenotypes. However, the extent to which these phenotypes share genetic architecture is unclear. This question is of great relevance to determining key risk factors for suicide, and to alleviate the societal burden of suicidal thoughts and behaviors (STBs). To help address the question of heterogeneity, consortia efforts have recently shifted from a focus on suicide within the context of major psychopathology (e.g. major depressive disorder, schizophrenia) to suicide as an independent entity. Recent molecular studies of suicide risk by members of the Psychiatric Genomics Consortium and the International Suicide Genetics Consortium have identified genome-wide significant loci associated with SA and with suicide death, and have examined these phenotypes within and outside of the context of major psychopathology. This review summarizes important insights from epidemiological and biometrical research on suicide, and discusses key empirical findings from molecular genetic examinations of STBs. Polygenic risk scores for these phenotypes have been observed to be associated with case−control status and other risk phenotypes. In addition, estimated shared genetic covariance with other phenotypes suggests specific medical and psychiatric risks beyond major depressive disorder. Broadly, molecular studies suggest a complexity of suicide etiology that cannot simply be accounted for by depression. Discussion of the state of suicide genetics, a growing field, also includes important ethical and clinical implications of studying the genetic risk of suicide.

scholarly journals Insights into Dyslexia Genetics Research from the Last Two Decades

2021 ◽  
Vol 12 (1) ◽  
pp. 27
Author(s):  
Florina Erbeli ◽  
Marianne Rice ◽  
Silvia Paracchini
Keyword(s):  
Language Disorder ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Genome Wide Association Studies ◽  
Genetics Research ◽  
Genome Wide ◽  
Genetic Risks

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field.

Construct validation using multitrait‐multimethod‐twin data: The case of a general factor of personality

2010 ◽  
Vol 24 (3) ◽  
pp. 258-277 ◽  
Author(s):  
Rainer Riemann ◽  
Christian Kandler
Keyword(s):  
Study Design ◽  
Convergent Validity ◽  
Structural Equation ◽  
Twin Studies ◽  
Higher Order ◽  
Genetic Effects ◽  
Order Structure ◽  
General Factor ◽  
General Factor Of Personality ◽  
Peer Report

We describe a behavioural genetic extension of the classic multitrait‐multimethod study design that allows estimating genetic and environmental influences on method effects in twin studies (MTMM‐T). Genetic effects and effects of the environment shared by siblings are interpreted as indicators of convergent validity. In an application of the MTMM study design, we used self‐ and peer report data to examine the higher‐order structure of the NEO‐PI‐R. Structural equation modelling did not support a general factor of personality in multimethod data. The higher‐order factor Stability turns out to be, at most, a weak trait factor. Genetic effects on method factors indicate that especially self‐reports but also peer reports show convergent validity between twins but not between methods. Copyright © 2010 John Wiley & Sons, Ltd.

Behavior and Molecular Genetics of Personality Disorders

2012 ◽  
pp. 142-165
Author(s):  
Susan C. South ◽  
Ted Reichborn-Kjennerud ◽  
Nicholas R. Eaton ◽  
Robert F. Krueger
Keyword(s):  
Personality Disorder ◽  
Personality Disorders ◽  
Molecular Genetics ◽  
Behavior Genetics ◽  
Association Studies ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Personality Pathology ◽  
Genome Wide Association Studies

The purpose of this chapter is to provide an overview of the behavior and molecular genetics of personality disorder. We begin with a thorough review of findings from the field of behavior genetics of personality pathology, including univariate twin studies, multivariate twin studies, and new models of gene–environment interplay. We then discuss the molecular genetics of personality pathology, including a consideration of candidate gene analysis, linkage analysis, and genome-wide association studies. We focus in particular on research concerning antisocial personality disorder (including antisociality and aggression), borderline personality disorder, schizotypal personality disorder, Cluster B and C personality disorders, and normal personality traits. We then provide a discussion of challenges and future directions with respect to behavior and molecular genetic research. We conclude the chapter with a discussion of the implications of this research for the forthcoming fifth edition of the American Psychiatric Association’s diagnostic manual.

Twin Studies of Political Behavior: Untenable Assumptions?

2008 ◽  
Vol 6 (4) ◽  
pp. 785-791 ◽  
Author(s):  
Jon Beckwith ◽  
Corey A. Morris
Keyword(s):  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
First Century ◽  
Behavioral Traits ◽  
Political Ideologies ◽  
Equal Environments Assumption ◽  
Twin Method ◽  
Genetic Techniques ◽  
Equal Environments

Using the “classical twin method,” political scientists John Alford, Carolyn Funk, and John Hibbing conclude that political ideologies are significantly influenced by genetics, an assertion that has garnered considerable media attention. Researchers have long used human twins in attempts to assess the degree of genetic influence on various behavioral traits. Today, this methodology has been largely replaced in favor of contemporary molecular genetic techniques, and thus heritability studies have seen a diminishing role in behavioral genetic research of the twenty-first century. One important reason the twin method has been superseded is that it depends upon several questionable assumptions, the most significant of which is known as the equal environments assumption. Alford, Funk, and Hibbing argue that this crucial assumption, and thus their conclusion, holds up under empirical scrutiny. They point to several studies in support of this assumption. Here, we review the evidence presented and conclude that these attempts to test the equal environments assumption are weak, suffering significant methodological and inherent design flaws. Furthermore, much of the empirical evidence provided by these studies actually argues that, contrary to the interpretation, trait-relevant equal environments assumptions have been violated. We conclude that the equal environments assumption remains untenable, and as such, twin studies are an insufficient method for drawing meaningful conclusions regarding complex human behavior.

Happiness and Wellbeing; the value and findings from genetic studies

2020 ◽  
Author(s):  
Margot Van de Weijer ◽  
Lianne de Vries ◽  
Meike Bartels
Keyword(s):  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Well Being ◽  
Future Directions ◽  
Genetic Studies ◽  
Global Trends ◽  
Genetic And Environmental Factors ◽  
Insight Into ◽  
Ageing Populations

In light of major global trends (e.g., rise of ageing populations, increasing longevity, decreasing birth rates), maintaining, facilitating, and building well-being (WB) is crucial, but also becomes increasingly complex and demanding. Over the past decade, twin studies have helped us get better insight into the extent to which genes and environments contribute to individual differences in well-being. Our knowledge about these genetic and environmental factors is continuingly growing with studies on well-being related phenotypes, extensions of twin studies, molecular genetic studies, and environmental studies. In this chapter, we provide an overview of past, present, and future directions of behavioural genetic research on well-being, happiness, and related phenotypes.

scholarly journals Molecular studies of identification of genes for osteoporosis: the 2002 update

2003 ◽  
Vol 177 (2) ◽  
pp. 147-196 ◽  
Author(s):  
YZ Liu ◽  
YJ Liu ◽  
RR Recker ◽  
HW Deng
Keyword(s):  
Association Studies ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Large Body ◽  
Current Status ◽  
Vdr Gene ◽  
Genetic Studies ◽  
Retrospective View ◽  
Genetics Of Osteoporosis ◽  
Trait Locus

We aim to give a comprehensive review, updated to 2002, of the most important and representative molecular genetic studies, performed mainly within the past decade, that aimed to identify the gene(s) involved in osteoporosis. Early reviews were largely confined to association studies in humans, but we review here, separately, the results of both association and linkage studies in humans, and quantitative trait locus (QTL) mapping in animal models. The main results of all the studies are tabulated for comparison and ease of reference, and to provide a comprehensive retrospective view of molecular genetics studies of osteoporosis. The most striking findings and the most representative studies are singled out for comment regarding the immediacy of their influence on present understanding of the genetics of osteoporosis and on the current status of genetic research in osteoporosis. This is particularly relevant for studies on the association of the vitamin D receptor (VDR) gene, for which there has been a large body of studies and reviews published. The format adopted by this review should be ideal for accommodating future new advances and studies in a fairly young field that is still developing rapidly.

General vs. Specific Vulnerabilities: Polygenic Risk Scores and Higher-Order Psychopathology Dimensions in the Adolescent Brain Cognitive Development (ABCD) Study

2020 ◽  
Author(s):  
Monika Waszczuk ◽  
Jiaju Miao ◽  
Anna Docherty ◽  
Andrey Shabalin ◽  
Giorgia Michelini ◽  
...  
Keyword(s):  
Externalizing Behavior ◽  
Higher Order ◽  
Genetic Effects ◽  
European Ancestry ◽  
Risk Scores ◽  
General Factor ◽  
Childhood Psychopathology ◽  
Polygenic Risk ◽  
Genetic Vulnerability ◽  
Specific Factors

Background. Polygenic risk scores (PRS) capture genetic vulnerability to psychiatric conditions and promise to advance our understanding of mental health etiology in children. Emerging evidence suggests that PRSs may be associated with higher-order dimensions of childhood psychopathology. The current study delineated a pattern of associations of major PRSs with an overarching general factor of psychopathology (p-factor), and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment.Method. The sample consisted of 4,717 unrelated children (mean age=9.92, SD=.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically-derived general factor and five specific factors. Partial correlations explored associations between psychopathology factors and major psychopathology-related PRSs originally discovered in large samples (Ns>100,000). Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.Results. Four PRSs were associated primarily with the general factor (>60% of genetic effects were general): Depression-PRS, Neuroticism-PRS, PTSD-PRS, and Insomnia-PRS. Two PRS contributed comparably to general and specific psychopathology: Smoking-PRS and Number of Sexual Partners-PRS. Five PRSs contributed primary to specific factors (<40% of genetic effects were general): Adventurousness-PRS, Disinhibition-PRS, Educational Attainment-PRSs, BMI-PRS, and Intelligence-PRS. The incremental associations with specific factors were mainly driven by the externalizing dimension. Conclusion. The PRSs for internalizing problems predominantly captured non-specific genetic vulnerability to psychopathology in children. Conversely, PRSs for externalizing problems contributed to more specific psychopathology outcomes, most notably externalizing behavior. Overall, many major PRSs captured both general and specific genetic vulnerability to childhood psychopathology.

scholarly journals Internet Cognitive Testing of Large Samples Needed in Genetic Research

2007 ◽  
Vol 10 (4) ◽  
pp. 554-563 ◽  
Author(s):  
Claire M. A. Haworth ◽  
Nicole Harlaar ◽  
Yulia Kovas ◽  
Oliver S. P. Davis ◽  
Bonamy R. Oliver ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Statistical Power ◽  
High Reliability ◽  
National Curriculum ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Reliability And Validity ◽  
Cognitive Testing ◽  
Cognitive Test ◽  
Large Samples

AbstractQuantitative and molecular genetic research requires large samples to provide adequate statistical power, but it is expensive to test large samples in person, especially when the participants are widely distributed geographically. Increasing access to inexpensive and fast Internet connections makes it possible to test large samples efficiently and economically online. Reliability and validity of Internet testing for cognitive ability have not been previously reported; these issues are especially pertinent for testing children. We developed Internet versions of reading, language, mathematics and general cognitive ability tests and investigated their reliability and validity for 10- and 12-year-old children. We tested online more than 2500 pairs of 10-year-old twins and compared their scores to similar internet-based measures administered online to a subsample of the children when they were 12 years old (> 759 pairs). Within 3 months of the online testing at 12 years, we administered standard paper and pencil versions of the reading and mathematics tests in person to 30 children (15 pairs of twins). Scores on Internet-based measures at 10 and 12 years correlated .63 on average across the two years, suggesting substantial stability and high reliability. Correlations of about .80 between Internet measures and in-person testing suggest excellent validity. In addition, the comparison of the internet-based measures to ratings from teachers based on criteria from the UK National Curriculum suggests good concurrent validity for these tests. We conclude that Internet testing can be reliable and valid for collecting cognitive test data on large samples even for children as young as 10 years.

scholarly journals Assessing the evidence for shared genetic risks across psychiatric disorders and traits

2017 ◽  
Vol 48 (11) ◽  
pp. 1759-1774 ◽  
Author(s):  
Joanna Martin ◽  
Mark J. Taylor ◽  
Paul Lichtenstein
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Architecture ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Future Research ◽  
Psychiatric Genetic ◽  
Genome Wide ◽  
Clinical Disorders ◽  
Genetic Risks

AbstractGenetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

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